Injury to the lung and chest is the most common factor leading to the development of respiratory failure. However, in some patients, normal blood gas tensions are maintained in the face of seriously impaired chest bellows function while in others, CO2 retention occurs with minimal decrements in function. Previous studies in man and animals indicate that altered gas exchange and changes in mechanical properties of the thorax bring into operation chemical and neural control systems which help compensate for injury. The overall objective of this program is to study the interplay of these neural and chemical control systems with the chest bellow in order to more clearly understand and improve the treatment of respiratory failure. The program includes complementary projects in man and in animals designed to evaluate neural and chemical responses to acute and chronic lung injury. The studies in man are designed to assess the effects of external mechanical loads on the output of respiratory controller and its discharge pattern in normal subjects and patients with lung disease. Respiratory motor neuron output will be assessed by measurements of ventilation, the force of respiratory muscle contraction and from recordings of respiratory muscle electrical activity. Additional aims of the studies in man are to compare the ability of normal subjects and patients to detect changes in external loads and in their own breathing. These studies will be useful in developing tests for the diagnosis of respiratory controller abnormalities and in devising methods for the early detection of such abnormalities.